JP4522262B2 - 化合物 - Google Patents

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Publication number

JP4522262B2

JP4522262B2 JP2004548887A JP2004548887A JP4522262B2 JP 4522262 B2 JP4522262 B2 JP 4522262B2 JP 2004548887 A JP2004548887 A JP 2004548887A JP 2004548887 A JP2004548887 A JP 2004548887A JP 4522262 B2 JP4522262 B2 JP 4522262B2

Authority

JP

Japan

Prior art keywords

dihydro

hydroxy

amino

oxo

pyrido

Prior art date

2002-06-26

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

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• 150000001875 compounds Chemical class 0.000 title claims description 183
• -1 isoquinolin-5-yl Chemical group 0.000 claims description 347
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 52
• 229910052739 hydrogen Inorganic materials 0.000 claims description 42
• 239000001257 hydrogen Substances 0.000 claims description 37
• 150000003839 salts Chemical class 0.000 claims description 32
• 229910052736 halogen Inorganic materials 0.000 claims description 25
• 150000002367 halogens Chemical class 0.000 claims description 25
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
• 150000002431 hydrogen Chemical class 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 7
• QURAWDWTNZXEDT-UHFFFAOYSA-N 2-methoxyquinolin-8-amine Chemical compound C1=CC=C(N)C2=NC(OC)=CC=C21 QURAWDWTNZXEDT-UHFFFAOYSA-N 0.000 claims description 6
• 241000124008 Mammalia Species 0.000 claims description 6
• JHIAOWGCGNMQKA-UHFFFAOYSA-N 2-methyl-8-quinolinamine Chemical compound C1=CC=C(N)C2=NC(C)=CC=C21 JHIAOWGCGNMQKA-UHFFFAOYSA-N 0.000 claims description 5
• 208000035143 Bacterial infection Diseases 0.000 claims description 5
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical compound C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 claims description 4
• DMBFCTCQROWGDZ-UHFFFAOYSA-N 8-aminoquinoline-2-carbonitrile Chemical compound C1=C(C#N)N=C2C(N)=CC=CC2=C1 DMBFCTCQROWGDZ-UHFFFAOYSA-N 0.000 claims description 4
• 150000001204 N-oxides Chemical class 0.000 claims description 4
• 125000004553 quinoxalin-5-yl group Chemical group N1=CC=NC2=C(C=CC=C12)* 0.000 claims description 4
• 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 claims description 3
• ODGSTKZGPNVNKR-QKSGUBBWSA-N (1R,3S,4R)-1-[(2-cyanoquinolin-8-yl)carbamoyl]-3-hydroxy-4-[(3-oxo-4H-pyrido[3,2-b][1,4]oxazin-6-yl)methylamino]cyclohexane-1-carboxylic acid Chemical compound C1C[C@@](C[C@@H]([C@@H]1NCC2=NC3=C(C=C2)OCC(=O)N3)O)(C(=O)NC4=CC=CC5=C4N=C(C=C5)C#N)C(=O)O ODGSTKZGPNVNKR-QKSGUBBWSA-N 0.000 claims description 2
• RRWFGHIMZGJJKU-UHFFFAOYSA-N 1-methoxyisoquinolin-8-amine Chemical compound C1=CC(N)=C2C(OC)=NC=CC2=C1 RRWFGHIMZGJJKU-UHFFFAOYSA-N 0.000 claims description 2
• JTNBYFVUXPHZIJ-UHFFFAOYSA-N 2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-amine Chemical compound O1CCOC2=C1N=CC=C2N JTNBYFVUXPHZIJ-UHFFFAOYSA-N 0.000 claims description 2
• CJIIYERJYXPGHA-UHFFFAOYSA-N 2-methylquinoxalin-5-amine Chemical compound NC1=CC=CC2=NC(C)=CN=C21 CJIIYERJYXPGHA-UHFFFAOYSA-N 0.000 claims description 2
• RPBQBSWZBRIJSO-UHFFFAOYSA-N 3-methoxyquinoxalin-5-amine Chemical compound C1=CC=C(N)C2=NC(OC)=CN=C21 RPBQBSWZBRIJSO-UHFFFAOYSA-N 0.000 claims description 2
• ANDGDEKVTJNURV-UHFFFAOYSA-N 4-aminoquinoline-6-carbonitrile Chemical compound C1=C(C#N)C=C2C(N)=CC=NC2=C1 ANDGDEKVTJNURV-UHFFFAOYSA-N 0.000 claims description 2
• DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical compound N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 claims description 2
• PJDFSPWLDZBWIX-UHFFFAOYSA-N 5-methoxyquinolin-4-amine Chemical compound C1=CC(N)=C2C(OC)=CC=CC2=N1 PJDFSPWLDZBWIX-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• CWXZEXZFHGYYCD-UHFFFAOYSA-N thieno[3,2-b]pyridin-7-amine Chemical compound NC1=CC=NC2=C1SC=C2 CWXZEXZFHGYYCD-UHFFFAOYSA-N 0.000 claims description 2
• MLHSEJGZQHDJSS-MIRXNBLZSA-N (1R,3R,4R)-1-[(2-cyanoquinolin-8-yl)carbamoyl]-3-hydroxy-4-[(3-oxo-4H-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxylic acid Chemical compound C1C[C@@](C[C@H]([C@@H]1NCC2=NC3=C(C=C2)SCC(=O)N3)O)(C(=O)NC4=CC=CC5=C4N=C(C=C5)C#N)C(=O)O MLHSEJGZQHDJSS-MIRXNBLZSA-N 0.000 claims 2
• MLHSEJGZQHDJSS-QKSGUBBWSA-N (1R,3S,4R)-1-[(2-cyanoquinolin-8-yl)carbamoyl]-3-hydroxy-4-[(3-oxo-4H-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxylic acid Chemical compound C1C[C@@](C[C@@H]([C@@H]1NCC2=NC3=C(C=C2)SCC(=O)N3)O)(C(=O)NC4=CC=CC5=C4N=C(C=C5)C#N)C(=O)O MLHSEJGZQHDJSS-QKSGUBBWSA-N 0.000 claims 1
• ODGSTKZGPNVNKR-RYGBOPQRSA-N (1S,3R,4S)-1-[(2-cyanoquinolin-8-yl)carbamoyl]-3-hydroxy-4-[(3-oxo-4H-pyrido[3,2-b][1,4]oxazin-6-yl)methylamino]cyclohexane-1-carboxylic acid Chemical compound C1C[C@](C[C@H]([C@H]1NCC2=NC3=C(C=C2)OCC(=O)N3)O)(C(=O)NC4=CC=CC5=C4N=C(C=C5)C#N)C(=O)O ODGSTKZGPNVNKR-RYGBOPQRSA-N 0.000 claims 1
• MLHSEJGZQHDJSS-RYGBOPQRSA-N (1S,3R,4S)-1-[(2-cyanoquinolin-8-yl)carbamoyl]-3-hydroxy-4-[(3-oxo-4H-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino]cyclohexane-1-carboxylic acid Chemical compound C1C[C@](C[C@H]([C@H]1NCC2=NC3=C(C=C2)SCC(=O)N3)O)(C(=O)NC4=CC=CC5=C4N=C(C=C5)C#N)C(=O)O MLHSEJGZQHDJSS-RYGBOPQRSA-N 0.000 claims 1
• XQOHGKZCTXPHMB-UHFFFAOYSA-N 1,6-naphthyridin-4-amine Chemical compound C1=NC=C2C(N)=CC=NC2=C1 XQOHGKZCTXPHMB-UHFFFAOYSA-N 0.000 claims 1
• TXZGIJQANGIGSE-UHFFFAOYSA-N 3-methylquinoxalin-5-amine Chemical compound C1=CC=C(N)C2=NC(C)=CN=C21 TXZGIJQANGIGSE-UHFFFAOYSA-N 0.000 claims 1
• KAVBUDPNQPEDNY-UHFFFAOYSA-N OC1(CCC(CC1)NCC=1C=CC=2SCC(NC2N1)=O)CCC=1C=CC=C2C=CC(=NC12)OC.O1NC(CC=C1)=O Chemical compound OC1(CCC(CC1)NCC=1C=CC=2SCC(NC2N1)=O)CCC=1C=CC=C2C=CC(=NC12)OC.O1NC(CC=C1)=O KAVBUDPNQPEDNY-UHFFFAOYSA-N 0.000 claims 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 204
• 239000007787 solid Substances 0.000 description 187
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 172
• 238000000034 method Methods 0.000 description 164
• 125000000217 alkyl group Chemical group 0.000 description 130
• 150000002500 ions Chemical class 0.000 description 124
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
• 239000000203 mixture Substances 0.000 description 110
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 105
• 239000000243 solution Substances 0.000 description 101
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 67
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
• 150000001412 amines Chemical class 0.000 description 64
• 238000006243 chemical reaction Methods 0.000 description 59
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 58
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
• 230000002829 reductive effect Effects 0.000 description 53
• 235000019439 ethyl acetate Nutrition 0.000 description 48
• 239000002253 acid Substances 0.000 description 41
• 239000000463 material Substances 0.000 description 37
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
• 235000019441 ethanol Nutrition 0.000 description 35
• 239000012458 free base Substances 0.000 description 35
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• 239000000741 silica gel Substances 0.000 description 33
• 229910002027 silica gel Inorganic materials 0.000 description 33
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 31
• 125000003118 aryl group Chemical group 0.000 description 30
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 27
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
• 150000001408 amides Chemical class 0.000 description 26
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 26
• 239000000284 extract Substances 0.000 description 26
• 239000003921 oil Substances 0.000 description 26
• 235000019198 oils Nutrition 0.000 description 26
• 125000003277 amino group Chemical group 0.000 description 25
• 125000000623 heterocyclic group Chemical group 0.000 description 23
• 238000005932 reductive alkylation reaction Methods 0.000 description 23
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
• 125000005090 alkenylcarbonyl group Chemical group 0.000 description 22
• 239000000047 product Substances 0.000 description 22
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 21
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 21
• 125000005843 halogen group Chemical group 0.000 description 21
• 230000008569 process Effects 0.000 description 21
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 20
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 20
• 239000002585 base Substances 0.000 description 20
• VEPGNAIYGRUSIA-UHFFFAOYSA-N 3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde Chemical compound S1CC(=O)NC2=NC(C=O)=CC=C21 VEPGNAIYGRUSIA-UHFFFAOYSA-N 0.000 description 19
• 150000002148 esters Chemical class 0.000 description 19
• 125000001424 substituent group Chemical group 0.000 description 19
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 18
• 229910005965 SO 2 Inorganic materials 0.000 description 18
• 238000001914 filtration Methods 0.000 description 18
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 18
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• 238000003756 stirring Methods 0.000 description 17
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 16
• 125000004429 atom Chemical group 0.000 description 16
• 238000004587 chromatography analysis Methods 0.000 description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• 229910052799 carbon Inorganic materials 0.000 description 15
• 229910052760 oxygen Inorganic materials 0.000 description 15
• 239000011541 reaction mixture Substances 0.000 description 15
• 238000010992 reflux Methods 0.000 description 15
• 125000005137 alkenylsulfonyl group Chemical group 0.000 description 14
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 14
• 125000004414 alkyl thio group Chemical group 0.000 description 14
• 239000000543 intermediate Substances 0.000 description 14
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
• 235000017557 sodium bicarbonate Nutrition 0.000 description 14
• 229910052717 sulfur Inorganic materials 0.000 description 14
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 13
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 13
• 125000003342 alkenyl group Chemical group 0.000 description 13
• 229910052757 nitrogen Inorganic materials 0.000 description 13
• 230000009467 reduction Effects 0.000 description 13
• 238000006722 reduction reaction Methods 0.000 description 13
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
• 239000012300 argon atmosphere Substances 0.000 description 12
• PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 11
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 11
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 125000003545 alkoxy group Chemical group 0.000 description 10
• 239000012267 brine Substances 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 10
• RUSTYNDGQSCBHW-UHFFFAOYSA-N cyclohex-3-ene-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CCC=CC1 RUSTYNDGQSCBHW-UHFFFAOYSA-N 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
• 239000012279 sodium borohydride Substances 0.000 description 10
• 229910000033 sodium borohydride Inorganic materials 0.000 description 10
• 238000003786 synthesis reaction Methods 0.000 description 10
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 9
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 125000002252 acyl group Chemical group 0.000 description 9
• 150000001540 azides Chemical class 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 238000007796 conventional method Methods 0.000 description 9
• 238000001816 cooling Methods 0.000 description 9
• 238000005859 coupling reaction Methods 0.000 description 9
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 125000005842 heteroatom Chemical group 0.000 description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
• 125000006574 non-aromatic ring group Chemical group 0.000 description 8
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
• 239000003981 vehicle Substances 0.000 description 8
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
• WOUDMBLIVQNGLP-UHFFFAOYSA-N [5-(2-methoxy-2-oxoethoxy)-4-nitropyridin-2-yl]methyl 2,2,2-trifluoroacetate 1-oxidopyridin-1-ium Chemical compound [N+]1(=CC=CC=C1)[O-].COC(=O)COC=1C(=CC(=NC1)COC(C(F)(F)F)=O)[N+](=O)[O-] WOUDMBLIVQNGLP-UHFFFAOYSA-N 0.000 description 7
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
• 229910021529 ammonia Inorganic materials 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• 229910002091 carbon monoxide Inorganic materials 0.000 description 7
• 239000003638 chemical reducing agent Substances 0.000 description 7
• 230000008878 coupling Effects 0.000 description 7
• 238000010168 coupling process Methods 0.000 description 7
• 238000001704 evaporation Methods 0.000 description 7
• 230000008020 evaporation Effects 0.000 description 7
• 230000007062 hydrolysis Effects 0.000 description 7
• 238000006460 hydrolysis reaction Methods 0.000 description 7
• 239000012280 lithium aluminium hydride Substances 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 6
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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